Cystic fibrosis (CF) is the most common lethal genetic disease in North America, affecting one in every 2500 individuals. Most of the morbidity and over 90 percent of the mortality results from chronic progressive inflammation of the lungs. Current therapies have proven unsuccessful at preventing the ultimate respiratory failure seen in these patients. When instilled into mouse lungs, DNA isolated from the sputum of patients with CF, has recently been shown to induce neutrophil migration, suggesting that CF DNA contributes to inflammation. Targeted Gene Delivery, Inc. has developed a proprietary recombinant protein that binds both bacterial and mammalian DNA. This SBIR Phase I proposal will test in an animal model, the feasibility of using this soluble protein as a treatment strategy to safely and effectively eliminate or reduce CF DAN-induced airway inflammation. The investigators speculate that this proprietary protein will bind to extracellular CF DNA in the airway, preventing CF DNA from binding to immune lung cells, and prevent subsequent induction of an inflammatory response. The company speculates this new treatment strategy, in combination with current anti-inflammatory strategies, may in the future prove effective in eliminating the chronic inflammation seen in patients with cystic fibrosis. PROPOSED COMMERCIAL APPLICATION: Targeted Gene Delivery, Inc. holds the exclusive rights to the sequence for a unique DNA binding protein (DNA-R) and for the use of this protein as a soluble receptor molecule to block DNA-induced inflammation. The DNA-R protein offers the opportunity for develoment of a specific product with therapeutic application to reduce or eliminate chronic and progressive DNA-induced lung inflammation seen in patients with cystic fibrosis.